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Category: Medicine, Drugs & Devices

While we have a healthy skepticism toward the pharmaceutical industry, former Obama adviser Ezekiel Emanuel’s attack in the New York Times on Big Pharma for not selling cancer drugs because they can’t make any money is long on accusation but short on facts: Continue reading Name that drug

Medicare and Medicaid will continue to pay for Avastin prescribed for breast cancer even though the drug offers no meaningful benefits — certainly none worth $88,000 per patient per year to taxpayers. It will be hard to control the Medicare entitlement if snake oil is to be made available on demand.

Why is the editor of the New England Journal of Medicine encouraging a cancer scare over the cholesterol-lowering drug Vytorin? Is he overcompensating for past bad behavior?

Prescribed for millions of patients, Vytorin is a single pill that combines the cholesterol-lowering medicines Zocor and Zetia. Its popularity declined in early 2008 after several studies questioned whether Vytorin produced any health benefit and a panel of cardiologists recommended that the drug be used only as a last resort.

Then, in July, a Norwegian researcher reported that, in a clinical trial known as SEAS, 102 patients taking Vytorin developed cancer, compared with 67 patients taking a placebo — a statistically significant result indicating that chance could be ruled out with some degree of confidence as the cause.

Drug companies Merck and Schering-Plough, the makers of Zocor and Zetia, respectively, subsequently commissioned famed epidemiologist Richard Peto of Oxford University to evaluate the SEAS results. Those findings were published this week on the Web site of the New England Journal of Medicine.

Based on his review of SEAS and two other ongoing Vytorin trials (called SHARP and IMPROVE-IT), Peto concluded that the trials provided no credible link between Vytorin and cancer risk, although follow-up would be needed to make a more reliable determination.

Peto based his conclusion on the fact that in the SEAS trial, there were no statistically significant increases in any specific type of cancer; the statistically significant result occurred only by adding all cancers together. Moreover, for the three specific cancers with reported risks closest to attaining statistical significance in the SEAS trial — skin, stomach and prostate — the results were precisely the opposite of what occurred in the SHARP and IMPROVE-IT trials. That is, in those trials, placebo patients had higher rates of cancer at those sites than did Vytorin users.

Additionally, Peto found no increase in risk of cancer over time in the three trials — generally, cancer risk increases with increasing exposure to a cancer-causing substance. This observation, he acknowledged, will also require more follow-up, since the patients in the trials have been followed for only a few years.

Although more Vytorin users than placebo patients died from cancer in all three trials, the result was only statistically significant in the SEAS trial. But Peto dismissed the SEAS result, since it was what had generated all the controversy in the first place and so couldn’t be used to verify the validity of a link between Vytorin and cancer. More telling than overall cancer deaths, however, was the lack of a statistically significant excess number of deaths from any specific type of cancer.

Though the available data don’t absolutely prove that Vytorin doesn’t increase cancer risk, there seems to be no good reason to think that it does — unless you’re the editor of the New England Journal of Medicine.

In an editorial accompanying the Peto analysis, editor Jeffrey Drazen wrote that, “Although the Oxford group may ultimately prove to be correct, it is appropriate to raise a note of caution.” Without providing any back-up scientific data, Drazen then speculated that since Vytorin works by interfering with the gastrointestinal absorption of cholesterol, it might also interfere with the absorption of other unnamed molecular entities that “could conceivably affect the growth of cancer cells.” Drazen also was unwilling to cede that higher cancer death rate of Zetia patients was simply due to chance “until further data are in.”

But the main reason that Drazen is simply wrong about keeping the Vytorin cancer scare on life support is that there’s no evidence whatsoever that the drug is associated with any specific form of cancer at any specific site.

For example, excessive smoking is associated with lung cancer, and occupational asbestos exposure is associated with mesothelioma. But given a specific route of exposure, no potential carcinogen is known to cause cancer at multiple sites on a random or haphazard basis. Aggregating different cancers into a catch-all “all cancer” category simply lacks demonstrable biological plausibility.

Drazen’s insistence on waiting for more data on cancer deaths is similarly nonsensical. Vytorin would first need to be associated with an increased risk of a death from a specific form of cancer — a notion clearly contradicted by the data so far.

None of this should be controversial or new to Drazen. So what’s up with him?

Prior to becoming editor of the New England Journal of Medicine, Drazen had close ties with many drug companies — and once got into trouble because of them.

In March 1999, the Food and Drug Administration found that Drazen made “false and misleading” statements about the safety and efficacy of the asthma drug levalbuterol made by Sepracor — a drug company that hired Drazen to review two studies on the drug and then to comment to a company interviewer. Needless to say, given this past, his NEJM appointment was somewhat controversial.

So since becoming editor, Drazen has seemingly gone out of his way to turn against the hand that once fed him. In a May 2005 Wall Street Journal article entitled, “Medical Editor Turns Activist On Drug Trials,” former NEJM editor Marcia Angell said that, “[Drazen’s] been converted. Through painful experience, Jeff is learning what these companies are about. He sees the ugly side that he hadn’t seen before — the bias that company-sponsored research contains, the suppression of results that they don’t like, the spin of unfavorable results.” Dr. Angell would apparently have us believe that Sepracor forced or tricked Drazen into saying “false and misleading” things about their drug.

So now it seems that instead of pro-drug company bias and spin, Drazen now leans toward anti-drug company bias and spin. Imagine if Drazen were just to stick to science in the first place. He wouldn’t have to worry about shifting alliances to atone for his mistakes.

Steven Milloy publishes JunkScience.com and DemandDebate.com. He is a junk science expert, and advocate of free enterprise and an adjunct scholar at the Competitive Enterprise Institute.

The government may tell asthmatics to “take a hit” for the environment. But that “hit” won’t be from their inhalers, which might be taken away.

A Food and Drug Administration advisory panel voted this week to recommend removing the “essential use” status that permits inexpensive, nonprescription asthma inhalers, like Primatene Mist, to remain on sale.

Powered by chlorofluorcarbon (CFC) propellants, the inhalers shoot epinephrine into the lungs of asthmatics, allowing them to breathe during potentially life-threatening asthma attacks. But environmentalists labeled CFCs a threat to the ozone layer in the 1980s, leading to an international phase-out of CFCs under the 1987 Montreal Protocol.

Nonprescription inhalers – and millions of asthmatics – have so far survived the Montreal Protocol because CFC use in inhalers is deemed to be “essential” and, therefore, exempt from the ban. Wyeth Consumer Healthcare estimates that 3 million Americans use its Primatene for mild or intermittent asthma and about 700,000 use Primatene alone because they can’t get prescriptions or lack health insurance, according to the Seattle Times (Jan. 25). Wyeth says that substitute non-CFC inhalers won’t be ready until 2009 or 2010 – and probably at a much higher cost.

But the FDA panel was apparently swayed by arguments that CFC-inhaler use threatens the ozone layer and public health. The hypothesis-of-hysteria is that CFCs thin the stratospheric ozone layer which, in turn, allows more solar ultraviolet (UV) radiation to reach the Earth’s surface which, in turn, increases the risk of skin cancer, cataracts and other health problems.
But asthmatics should not have to gasp for air because of this guesswork.

First, accepting for argument’s sake that ozone depletion alarmism is justified, only a trivial amount of CFCs would be released into the atmosphere due to inhaler use. No detectable damage to the ozone layer would likely result.

Global CFC production peaked pre-ban at over 1 million metric tons. But in 1999, for example, the U.S. requested an “essential use” exemption of only about 4,000 metric tons for inhalers – hardly a return to the old days when CFCs were used in a wide range of consumer and industrial products.

Back to the real world, however, the ozone depletion hypothesis has a great big hole of its own.

No one disputes the basic chemistry of ozone depletion – chlorine atoms from CFCs released into the environment can find their way into the stratosphere where they can chemically react with and “destroy” ozone.

It should be noted, however, that CFCs aren’t the only source of chlorine atoms in the stratosphere – Mother Nature, in fact, may supply most of them. Also, ozone is also continually being created so we won’t ever run out of ozone.

In any event, none of the alleged environmental and public health horrors of CFC-induced ozone “destruction” have ever been observed despite extensive study – one of the best kept secrets of environmentalism.

While overexposure to UV is a risk factor for some types of skin cancer and cataracts, no scientific study has ever demonstrated a link between ozone depletion and such overexposure or any health effects.

A December 2003 article in the journal Photochemical & Photobiological Sciences, for example, would only go so far as to say that “The potential health effects of elevated levels of ambient UV-B radiation are diverse, and it is difficult to quantify the risks.”

The absence of evidence linking ozone layer thinning with health effects isn’t surprising because the phenomenon was never thought (by experts, anyway) to lead to more than a trivial (10 percent) increase in UV radiation reaching the Earth’s surface.

As there is about a 5000 percent increase in UV radiation moving from the poles to the equator, a 10 percent increase in the mid-latitudes equates to a move 60 miles to the south – “hardly a source for health concerns,” says physicist Dr. S. Fred Singer of the Science and Environmental Policy Project.

It’s not even clear that ozone depletion, in its pre-phaseout heyday, ever increased the amount of UV radiation hitting the Earth’s surface. “There has been, of course, a determined search for a secular increase in [UV radiation] to match the presumed depletion of ozone. But no such trends had been observed,” says Dr. Singer.

And a little common sense about UV radiation goes a long way. Life flourishes in the tropics where UV radiation levels are far higher than in the quite inhospitable polar regions.

Yes, there is an “ozone hole,” but that label is more appropriately applied to the Montreal Protocol than the ever-changing thickness of the ozone layer over the Antarctic polar region.

Former Vice President “Ozone Al” Gore acknowledged in a recent presentation I attended that the real value of the Montreal Protocol was that it demonstrated the global political power of the environmental movement.

But while getting a junk science-fueled international treaty signed may have been a valuable political exercise for environmentalists, the Montreal Protocol can hardly be considered a success if it winds up needlessly depriving asthmatics of available, affordable and effective medication.

Steven Milloy publishes JunkScience.com and CSRwatch.com, and is an adjunct scholar at the Competitive Enterprise Institute.

The media and stock market are again atwitter with news of another supposed cancer breakthrough. Avastin (search), a drug developed by biotech giant Genentech (search), reportedly extended the median survival time of terminally ill colon cancer patients in a clinical trial by 4.7 months.

The news was formally released at last weekend’s meeting of the American Society of Clinical Oncology (search) (ASCO). The price of Genentech stock has risen by about 65 percent since mid-May when the news began leaking.

One biotech analyst said annual sales of Avastin could reach $2 billion as almost 150,000 Americans are diagnosed with colon cancer and 57,000 die from it every year.

And based on headlines such as the Los Angeles Times’ “New Drug Combinations Effective on Colon Cancer,” the Avastin claims sound exciting.

But since cancer breakthrough news is usually more smoke than fire, a closer look is warranted — especially since Avastin wasn’t effective in an earlier breast cancer trial.

It’s too bad a closer look isn’t possible.

Detailed information in standard study form about the Avastin trial isn’t available — not from the Duke University Medical Center, whose news release claimed Avastin’s efficacy was “proved,” and not from Genentech, whose market value increased by $15 billion on the news.

Both were happy to be contacted about the study, no doubt expecting more giddy and gullible reporting. But no detailed write-up was available. The Genentech spokesperson couldn’t even say when a study might be published.

Only a brief study summary or abstract was available, one omitting or glossing over key information and basic questions about the trial.

The trial involved 925 patients. About 800 patients were either given Avastin plus a standard chemotherapy or the chemotherapy alone. Another 100 patients were given Avastin in combination with another standard chemotherapy.

The abstract only contains results for the 800-patient treatment group. What happened in the 100-patient treatment group? Was Avastin effective there, too? If so, why not report it?

Avastin reportedly increased survival time by almost five months. But that claim relies on the major assumption that at the beginning of the trial, patients in the Avastin group, on average, had a similar expected survival time as patients in the chemotherapy-alone group.

Individual study subjects, though, likely had different types of colon cancer and were at different stages in the progression of their colon cancers. If the Avastin treatment group was, on average, at an earlier stage of colon cancer or had less aggressive colon cancers and metastases, it wouldn’t be surprising that their survival time is longer.

The researchers apparently hoped that random assignment of subjects to the Avastin and non-Avastin treatment groups would equalize the expected survival times of the treatment groups at the trial’s beginning.

This may have worked, but we just don’t know. Without some information about, and validation of the assumption, the touted results are based on a huge leap of faith.

The trial was multicenter in nature, meaning that patients were treated at several locations around the country. Such decentralization may give rise to a phenomenon known as “multicenter bias,” where the results from one study center may be skewed because of some systematic difference in the conduct of its part of the trial.

We can’t tell whether multicenter bias occurred in the Avastin trial because the data weren’t reported by a study center.

I asked lead researcher Herbert Hurwitz whether the study was peer-reviewed. He said it was reviewed by a committee of ASCO — the group putting on the medical conference where the results were announced.

But how could the committee perform a credible review with only the superficial abstract? No reputable journal would publish results without more. We must also wonder if the committee was truly objective since ASCO may have been eager to have such headline-grabbing claims announced at its annual meeting.

One final reason for requiring something more than “science by press conference” is that the biological mechanism by which Avastin is supposed to work, the blocking of blood vessels in tumors (anti-angiogenesis), hasn’t really panned out yet.

Based on studies in laboratory animals, anti-angiogenesis drugs were first touted several years ago in a front-page New York Times article that caused dramatic speculation in biotech stocks. But subsequent studies in humans have disappointed and biotech stock prices collapsed.

Given the huckster-ish history of anti-angiogenesis drug claims, Genentech and Hurwitz should realize more than a vague abstract is needed to show Avastin works. A detailed study would be a start, followed by more clinical trials.

Proven effective or not, terminally-ill cancer patients shouldn’t be denied Avastin or any other potentially helpful drug they are willing to try on their own dime. But cancer treatments shouldn’t be hailed until they are actually proven to work.

Steven Milloy is the publisher of JunkScience.com, an adjunct scholar at the Cato Institute and the author of Junk Science Judo: Self-defense Against Health Scares and Scams (Cato Institute, 2001).

Women have been scared during the last several weeks with new studies about alleged health risks from hormone replacement therapy (HRT). This scare contrasts starkly with the preceding decades of HRT being touted as the fountain of youth.

What should women and their physicians believe? Past hype? Recent hysteria?

Neither.

HRT, originally estrogen alone and later estrogen in combination with progestin, was approved in 1942 by the Food and Drug Administration to relieve the short-term symptoms of menopause such as night sweats and hot flashes.

Two decades later, though, HRT began being touted as a wonder drug for many long-term health concerns of women, not just menopausal symptoms. HRT mania was kicked off by Dr. Robert Wilson’s 1966 book Feminine Forever. Unknown at the time, the book was financed by Wyeth-Ayerst, the leading manufacturer of HRT.

Studies appeared in the scientific literature touting HRT as reducing bone loss, the risk of heart disease and the risk of some cancers.

But anyone who paid attention to the data rather than the hype would have known that these studies didn’t at all demonstrate HRT to be a panacea.

The studies invariably reported weak statistical correlations between HRT use and long-term health benefits — and that’s with the study populations biased in favor of the reported results.

The study populations taking HRT tended to be comprised of thinner, wealthier and better-educated women under physician care. It is not surprising that these women were healthier than the women in the “control” groups.

Myths about the long-term benefits of HRT nevertheless took hold. Premarin, the most popular HRT made by Wyeth-Ayerst, was recently used by about 12 million women in the U.S. at a cost of about $180 per year.

The New York Times quoted a female physician stating, “I may have taken my last pill this morning.”

But the most notable of the recent studies reported that, among 8,506 estrogen-plus-progestin HRT users, there was only a 29 percent increase in heart disease occurrence. The result was barely statistically significant, meaning there’s a worrisome possibility it was a fluke.

The study reported only a 26 percent increase in breast cancer occurrence. That result wasn’t statistically significant.

The study’s reported results for other health concerns were of similar magnitude and statistical significance — that is to say, weak.

But you don’t have to accept my characterization of such results.

As the National Cancer Institute points out: “In epidemiologic research, [risks of less than 100 percent] are considered small and usually difficult to interpret. Such increases may be due to chance, statistical bias or effects of confounding factors that are sometimes not evident.”

In other words, these results should be treated as preliminary — particularly until they are replicated many times by independent researchers. That’s just Scientific Method 101.

Moreover, these women were only studied for five years and previous studies report contradictory results. It seems the panic is premature.

David Sturdee, former chairman of the British Menopause Society, once said: “A lot of nonsense is talked by those who say HRT is the best thing since sliced bread. Equally, I am incensed by the idea that all HRT is unsafe. Some women feel undue pressure either to take HRT or not to.”

What kind of pressure? Wyeth-Ayerst pressed women to take HRT. Now others are trying to scare women about HRT.

Pharmaceutical manufacturer Eli Lilly promoted HRT fears in the fall of 1997 as it awaited approval of it rival drug, raloxifene (Evista).

Lilly placed full-page advertisements in women’s magazines that ominously read, “Many women have serious worries about a possible link between estrogen replacements and cancer.” The implication was that Evista didn’t increase cancer risk.

This marketing-by-scaremongering was eventually brought to a halt by a federal judge who issued an injunction against Lilly touting research that did not prove Evista prevented breast cancer.

No one disputes the short-term benefits of HRT for menopausal symptoms. Moreover, there is no substitute for it. But HRT’s supposed long-term benefits and risks so far seem to have more to do with unscrupulous marketing than science.

Deerfield-based Baxter Healthcare has been vindicated on a major health scare. But don’t expect to read about it in the media. It’s more fun to scare readers about vinyl IV bags causing cancer than it is to set the record straight. Continue reading Vinyl IV Bags: Media lose message

I hate to admit it. But I’m at that age where prostate cancer enters the mind – especially since my father just completed a course of radiation treatment for his prostate cancer.

Prostate cancer is the most commonly diagnosed cancer among U.S. men. And at about 40,000 annual deaths, it is the second deadliest behind lung cancer. Prostate cancer is the male version of breast cancer. It’s not preventable and early detection is the key to survival. But – and it’s a big “but” – controversy has arisen over early detection.

The prostate is a chestnut-sized gland in the make pelvic area. It plays a role in generating seminal fluid that helps transport sperm. For unknown reasons, the gland can enlarge and cancer can develop. Some cancers are fatal. Some aren’t. While most prostate cancer occurs in older men, it can strike younger men as well. Half of prostate cancer deaths occur in men over the age of 75. Fewer than 5 percent of deaths occur in men who were under 60 at diagnosis.

Until about 10 years ago, prostate cancer was detected by a technique euphemistically named the “digital rectal exam.” But rectal exams often don’t catch cancers until after they have spread – at which point it may be too late to cure. Then came the PSA test, a blood test that measures the level of prostate specific antigen. PSA is usually elevated in men with prostate cancer, but can also be elevated, usually to a lesser degree, in men with benign prostate growth.

The PSA test did wonders for diagnosing prostate cancer. The number of men diagnosed with prostate cancer in 1985 was about 85,000. By 1996, the number diagnosed had jumped to almost 320,000. Sounds great right? It was early detection we needed and early detection we got. But maybe not.

Though more prostate cancer is being detected now than 10 years ago, it’s not that more men are getting prostate cancer. It’s just that more prostate cancer is being detected by the PSA test. Not all prostate cancer is fatal. In older men, prostate cancer can be slow-growing so that they will die with it, not of it.

An elevated PSA test does not automatically mean that cancer is present. Like the digital rectal exam, a PSA a test can erroneously indicate prostate cancer and erroneously fail to detect a prostate cancer. So while the screening may lead to life-extending diagnosis and treatment, it can also lead to treatment of cancers that don’t need to be treated – or even cancer that a man may choose not to treat. Treatment may cause urinary incontinence or impotence.

Several years ago, controversy arose over whether routine screening for prostate cancer.

The American College of Physicians says that routine prostate-cancer screening “is not for everyone” and that it is “a complex decision that patients should make after talking to their physician, understanding the risks and benefits, and coming to an informed, individualized decision. A urologist said in the British Medical Journal that [PSA testing] “merely Promotes Stress and Anxiety.”

But the American Urology Association and the American Cancer Society recommend that, annual PSA testing be done annually beginning at age 50, and earlier for men at high risk. The developer of the PSA test, Dr. William J. Catalona, professor and chief of urology and the Washington University School of Medicine says “PSA testing has exhibited all the features of an effective cancer-screening tool.” But note that he didn’t say it saves lives. Why? Because there’s no proof it has.

The National Cancer Institute criticized the American Cancer Society in 1992 for acting hastily in recommending routine screening without waiting for proof that mass screening reduces mortality. The ACS’ chief medial officer offered the weak defense that “Physicians and the public are demanding to be told what to do.”

Until recently, there have been no controlled studies on whether PSA testing reduces the prostate cancer death rate. The first clinical trial to examine the value of PSA screening, released in May 1998, reported that PSA screening led to a 69 percent reduction in prostate cancer death rates. While sounding impressive, researchers immediately raised questions about potential bias in the study data. Men who agreed to be screened may have been healther than those who did not agree.

Now, a new study in the Oct. 6 Journal of the National Cancer Institute reports that PSA levels may mean something entirely different than originally thought.

So what do you do? How do you choose between the American College of Physicians and the American Urological Association? Does it help to know that the ACP recommendation is “evidenced-based”? The ACP examined and reviewed more than 40 studies to determine the potential benefits of screening, the complication rate of treatment, and the balance of benefits harms and costs. In contrast, the AUA recommendation represents a consensus of expert opinion. Evidence vs. expert opinion? Wouldn’t you think expert opinion would be based on evidence? Confused? As my father-in-law, a prominent south Florida urologist said, “Urologists have the most experience, but they also have the most to gain from routine screening.”

What do urologists have to gain? You decide. PSA testing costs about $100. An elevated PSA could lead to more testing or a biopsy costing around $1,500. The prostate testing market is worth about $200 million to $300 million annually. Until recently, the developer of – and the leading cheerleader for – the PSA test, William Catalona, was receiving $1 million per year “to study the effectiveness of the PSA test,” largely from Hybritech, a pharmaceutical firm that manufactures the PSA test.

Recently, Catalona criticized the American College of Physicians for recommending against routine screening in favor of physicians and patients discussing the potential benefits and known harms of screening diagnosis and treatment and making individual decisions. Catalona wrote “This sounds reasonable but is impractical because busy doctors lack time for long discussions.”

Prostate cancer can be life-threatening. If your physician doesn’t have the time to discuss your options, get a new doctor. And whatever you do, don’t fall for the unproven and undeciphered PSA test.